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PMID: 15254092 Published · ppublish English Comparative Study Journal Article Research Support, U.S. Gov't, P.H.S.

The rate of cocaine administration alters gene regulation and behavioral plasticity: implications for addiction.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 24 ·No. 28 ·2004-07-14 ·Pages 6362-70

Samaha AN, Mallet N, Ferguson SM, Gonon F, Robinson TE

Abstract

The rapid delivery of drugs of abuse to the brain is thought to promote addiction, but why this occurs is unknown. In the present study, we characterized the influence of rate of intravenous cocaine infusion (5-100 sec) on three effects thought to contribute to its addiction liability: its ability to block dopamine (DA) uptake, to activate immediate early gene expression, and to produce psychomotor sensitization. Rapid infusions potentiated the ability of cocaine to block DA reuptake, to induce c-fos and arc mRNA expression, especially in mesocorticolimbic regions, and to produce psychomotor sensitization. Thus, the rate at which cocaine is delivered influences both its neurobiological impact and its ability to induce a form of drug experience-dependent plasticity implicated in addiction. We propose that rapidly delivered cocaine may be more addictive, in part, because this more readily induces forms of neurobehavioral plasticity that lead to the compulsive pursuit of drugs.

MeSH Terms
Animals Behavior, Animal/drug effects Brain/drug effects,metabolism Cocaine/administration & dosage,pharmacology,toxicity Cocaine-Related Disorders/etiology Cytoskeletal Proteins Dopamine/metabolism Dopamine Uptake Inhibitors/administration & dosage,pharmacology,toxicity Drug Administration Schedule Frontal Lobe/drug effects,metabolism Gene Expression Regulation/drug effects Genes, Immediate-Early/drug effects Genes, fos/drug effects Immediate-Early Proteins/biosynthesis,genetics In Situ Hybridization Infusions, Intravenous Limbic System/drug effects,metabolism Locomotion/drug effects Male Neostriatum/drug effects,metabolism Nerve Tissue Proteins/biosynthesis,genetics Nucleus Accumbens/drug effects,metabolism Prefrontal Cortex/drug effects,metabolism Proto-Oncogene Proteins c-fos/biosynthesis,genetics Rats Rats, Sprague-Dawley
Chemicals
Cytoskeletal Proteins Dopamine Uptake Inhibitors Immediate-Early Proteins Nerve Tissue Proteins Proto-Oncogene Proteins c-fos activity regulated cytoskeletal-associated protein Cocaine Dopamine
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Samaha Anne-Noël
Department of Psychology (Biopsychology Program), University of Michigan, Ann Arbor, Michigan 48109-1109, USA.
Mallet Nicolas
Ferguson Susan M
Gonon François
Robinson Terry E
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.1205-04.2004
Published
2004-07-14
Pages
6362-70
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6729536
Subset
IM
Grants
NIDA NIH HHS · R37 DA04294 · United States
NIDA NIH HHS · R37 DA004294 · United States
NIDA NIH HHS · F31 DA14737 · United States
NIDA NIH HHS · K05 DA000473 · United States
NIDA NIH HHS · F31 DA014737 · United States
NIDA NIH HHS · T32 DA007267 · United States
NIDA NIH HHS · K05 DA00473 · United States
NIDA NIH HHS · T32 DA 07267 · United States
External Links
PubMed source DOI: 10.1523/JNEUROSCI.1205-04.2004 PMC Full Text View journal details
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